Date of Award
Winter 2024
Project Type
Dissertation
Program or Major
Chemistry
Degree Name
Doctor of Philosophy
First Advisor
John Tsavalas
Second Advisor
Aylin Aykanat
Third Advisor
Glen Miller
Abstract
Many plants and animals that live in arctic regions possess biological cryoprotecting agents (CPAs) known as antifreeze proteins (AFPs) which protect them against cryoinjury in their native subfreezing environment. AFPs and their synthetic biomimetics have received increasing attention as potential candidates for various industrial and bio-medical applications. Despite the interest in developing synthetic, macromolecular CPAs; a full understanding of the antifreeze process induced by these remains elusive. To explore this, we have synthesized a series of water- soluble polyol-based polymers with systematic variation of their chain architectures.While AFPs are well-known for their ice nucleation and recrystallization inhibition activity along with controlling the ice crystal morphology, the contrasting behavior of ice nucleation promotion by AFPs and its key contribution to the antifreezing process has not been fully explored. To this end, silver iodide (AgI) was used as an ice nucleator in different polyol-based polymer solutions in ultra-pure water (UPW), which imitated the ice nucleation process by AFPs. The polymer solution in UPW containing AgI dispersion showed significant improvement in IRI activity compared the same polymer solutions in PBS buffer. Our results demonstrated the considerable contribution of the ice nucleator in ice nucleation rate and temperature which enhance IRI activity of synthetic antifreeze polymers as the polymers could then stabilize smaller crystals earlier in their growth trajectory. The design of efficient, synthetic cryoprotecting agents is also critical to facilitating the recovery of frozen tissue and cells after cryo-storage. It has proven difficult to develop biomimetic cryoprotecting agents that exhibit ice recrystallization inhibition (IRI) activity, thermal hysteresis activity (THA), and dynamic ice shaping (DIS) abilities as strongly as native antifreeze glycol proteins. One polymer that does exhibit similar IRI, THA, and DIS potency is poly(vinyl alcohol) (PVA) derived glycerol-grafted-poly(vinyl alcohol) (G-g- PVA). While G-g-PVA has been demonstrated to show remarkable potency in these key areas, owing to the presence of a 1,2 diol in its pendent group, its widescale implementation has proven to be difficult resulting from the unreliable synthetic method utilized for its production. To this end we have developed a series of diol containing monomers that mimic the monomeric binding structure of G-g-PVA. We have additionally discovered the critical role of pendent group tether length, through the incorporation of ethylene glycol spacers, on cooperative polymer ice-surface interaction. Finally, as a sub-project relevant to the NH BioMade effort and biomaterial applications, we prepared four series of water-soluble poly(N-isopropylacrylamide) (pNIPAM), with well controlled molecular weights and end group chemistries, synthesized via reversible addition fragmentation chain-transfer (RAFT) polymerization. The effect of end-group chemistry on the thermal phase transitions (critical solution temperature) of aqueous solutions of these pNIPAMs were studied by differential scanning calorimetry (DSC) as a function of both molecular weight and concentration. We observed that increasing the hydrophilicity of the end-group significantly increased the phase transition temperature of low molecular weight polymer (10 kDa) but did not increase the transition temperature of the larger polymers (40 kDa) at lower concentrations. However, the presence of two terminal, hydrophilic groups significantly increased the concentration dependence of polymers at both molecular weights. This, we found was influenced by the macromolecular self-assembly of this type of system where the resulting morphology influenced the nature of the phase transition and its concentration dependence. We found that the assembled structures exhibited a bimodal thermal transition owing to the two regions of differing polymer chain density. These findings will contribute to the advancement of the design and application of biotechnological devices. In particular, they hold significant potential for the field of thermoresponsive drug delivery systems, as the two-step thermal transition of these assembled structures could enable precise targeted delivery of therapeutic agents
Recommended Citation
Mitchell, Nick, "Rational Design of Polymers for Specific Interactions with Liquid and Solid-State Water" (2024). Doctoral Dissertations. 2888.
https://scholars.unh.edu/dissertation/2888